Neoplastic cells utilize glycolysis to satisfy their increased needs for energy and biosynthetic precursors. The PFKFB enzymes (PFKFB1-4) synthesize fructose-2,6-bisphosphate (F2,6BP). F2,6BP activates 6-phosphofructo-1-kinase (PFK-1), a control point in the glycolytic pathway. Broadly, there remains a need to find better treatments for cancer, including but not limited to those that use PFKFB4 inhibitors.
Certain embodiments of the invention address one or more of the deficiencies described above. Some embodiments of the invention include inventive compounds. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Other embodiments include PFKFB4 inhibitors and methods of using the same that can target neoplastic cells, including, such as, mechanisms within those cells that relate to the use of the glycolytic pathway. In other embodiments, small molecule PFKFB4 inhibitors are used to disrupt the kinase domain of PFKFB4 and, in some instances, decrease the glucose metabolism and growth of human cancers. In other embodiments, the PFKFB4 inhibitors are selective for PFKFB4, and should not directly inhibit PFKFB1, PFKFB2, and PFKFB3. In yet other embodiments, the PFKFB4 inhibitor can have good oral bioavailability while sometimes reducing or avoiding toxicity. Additional embodiments of the invention are also discussed herein.